We have been successful in developing through selective breeding two lines of Hereford cattle with different pulmonary vascular responses to hypoxia. One called "susceptible" develops severe pulmonary hypertension and right heart failure at high altitude while the other known as "resistant" develops only moderate pulmonary hypertension and no heart failure. We have also initiated a program to develop a similar model in miniature swine using the same approach. Our studies for the next year in the bovine model will be directed toward answering two main questions. Do the susceptible cattle develop greater hypoxic pulmonary hypertension than the resistant cattle because their pulmonary blood vessels are more reactive or responsive to a given hypoxic stimulus or do they experience a greater hypoxic stimulus? Our specific aims are to determine whether the susceptible cattle as compared to the resistant cattle: a) have thicker-walled pulmonary arterioles based on histological studies of biopsied lung tissue, b) have more reactive pulmonary vessels as determined by in vivo and in vitro dose-response curves of the pulmonary pressor responses to increasing levels of vasoactive drugs and graded hypoxia, and c) hypoventilate or have a lesser hypoxic ventilatory drive to a given hypoxic stimulus. Results of our research could be of considerable importance to human and animal health. BIBLIOGRAHIC REFERENCES: Will, D. H., Hicks, J. L., Card, C. S., Reeves, J. T. and Alexander, A. F., 1975. Correlation of Acute with Chronic Hypoxic Pulmonary Hypertenson in Cattle. J. Appl. Physiol., 38:495-498. Will, D. H., Hicks, J. L., Card, C. S. and Alexander, A. F., 1975. Inherited Susceptibility of Cattle to High Altitude Pulmonary Hypertension. J. Appl. Physiol., 38:491-494.